... phagocytosis through Kupffer and endothelial cells Changing the size and lipid composition of the sphere can alter the biodistribution to the different cell populations within the liver This allows ... the fact thatthe irradiation is cytotoxic, thereby stimulating division of the surviving cells Nonviral Vectors Liposomes Liposomes are microscopic vesicles consisting of one or multiple aqueous ... compartments DNA is incorporated in the aqueous phase or associated with the lipid material after simply mixing with the lipid components Liposomes enter the liver by the portal circulation Their clearance...
... Mocs1-deficient mice until day 40 with periodic intrahepatic injections of purified cPMP from Escherichia coli [8] to achieve a suitable size for tail vein injection Intrahepatic injections were done ... end, we investigated the feasibility of successful rAAV re-administration at different time points in the MoCo deficient mouse model and compared the reapplication possibilities in different ... This is indirect evidence thatthe intravenous tail vein injections did not result in germ line transmission of the vector genome To estimate the necessary dosage for the treatment of humans, we...
... is a thermodynamic equilibrium based upon the amino Fig Predicted interactions between DGJ andthe active-site of aGal A DGJ is a known active-site directed competitive inhibitor of a-Gal A Interactions ... domain (amino acid residues 32–330), and a C-terminal domain (residues 331– 429) containing eight antiparallel b strands on two sheets in a b sandwich (Fig 1A) [28] The first domain contains the ... defective biosynthesis, loss of kinetic capability, excessive degradation of mutant protein, or their combinations During the course of examining the primary cause for deficient enzyme activity, Ishii...
... Preclinical Studies Initial retroviral gene transfer into murine hematopoietic repopulating cells was achieved in 1984 The discovery, availability, and application of various hematopoietic growth ... similar approach has been utilized in patients with EBV-LPD with the modification of incorporating the herpes simplex virus thymidine kinase (HSV-tk) gene into the retroviral vector This suicide ... converts the nontoxic prodrug ganciclovir to a toxic metabolite that kills the tk-expressing cell by inhibition of DNA synthesis The inclusion of this gene in vectors allows elimination of transduced...
... transfer will serve as the defining approach Rather, it will be the use of all available techniques, either individually or in combination, that will shape the application of this therapy Over the past ... conditions that have resulted in an inadequate endogenous neovascularization response in patients suffering from myocardial and lower limb ischemia Despite these limitations, angiogenic gene therapy ... ANGIOGENESIS 189 FIGURE 8.2 Inhibition of neointimal hyperplasia by in vivo gene transfer of endothelial cell–nitric oxide synthase (ecNOS) in balloon-injured rat carotid arteries See color insert...
... stimulating an anti-HIV-1 immune response; and (iii) inhibition of virus replication; these anti-HIV-1 strategies are aimed at the intracellular inhibition of virus replication (Table 11.2) All ... increase their stability (half-life) within a cell A variety of synthetic antisense oligonucleotides have been designed that inhibit the replication of HIV-1 However, their use for the inhibition ... transcription factor that interacts with Rev by binding to the Rev activation domain The interaction between mutants of the eIF-5A and Rev can effectively inhibit HIV-1 replication in vitro Utilization...
... of IL-5 messenger ribonucleic acid (mRNA), afforded protection against viral infections, and significantly decreased airway inflammation and airway hyperresponsiveness In this article, we investigated ... upregulates the IL-13Ra2 decoy receptor, leading to diminished IL-13 signaling31 and reduced goblet cell hyperplasia and eosinophilia.32 IFN-c significantly inhibits release of leukotrienes from peripheral ... procollagen Iand III and decreases fibrosis in a mouse model of bleomycin-induced lung injury.35 Exogenously supplied cytokines, such as IFN-c, IL-12, and IL-18, have a short half-life in vivo, and...
... probability of relapse Marked improvements of disease activity, functional ability, and quality of life were seen in the majority of juvenile idiopathic arthritis patients, resulting in restoration ... while allogeneic HSCT in another patient also resulted in a remission of RA [33] Allogeneic HSCT offers the theoretical benefit of replacing the autoaggressive immune system and utilizing the ... antibodies or total body irradiation The final step is reinfusion of the (autologous) graft with or without prior manipulation ex vivo The second step is the key therapeutic component, yet the initial...
... Academic detailing only; Academic detailing plus a message to the physician in the clinical decision support system asking the clinician to reconsider the aspirin therapy; and Academic detailing, ... is not clinically significant; therefore, the ability to show an even smaller statistically significant change indicates that this study has enough power to detect meaningful change in aspirin ... provider concerning their use of aspirin for primary prevention The academic detailing consisted of a presentation to the clinicians and staff of each office by the study principal investigator and...
... addressing The key problem of efficiency can be considered in terms of either improving vectors or overcoming biological barriers An intrinsic function of the lining epithelium of the airways is ... airways rather than the alveoli These include both the larger bronchial regions lined by a pseudostratified columnar epithelium and containing numerous submucosal glands, andthe small bronchiolar ... superficial epithelium is abundant and displays the ion transport defects in patients with CF, the submucosal glands are the cells expressing the highest CFTR levels in the lung and might well...
... increases, we did not expect high levels of circulating EPO Instead, we believe that a statistically significant difference in hematocrit, which is the real physiological parameter we want to impact ... the treated animal This strategy allows to avoid the deleterious initial hematocrit peak and to maintain a normal hematocrit with small fluctuation amplitude Furthermore, we may hypothesise that ... mice per group were used for the higher plasmid dose experiment, and eight Hbb-thal1 mice per group were used for the lower plasmid dose experiment Mice were first anaesthetised by intra-peritoneal...
... bilirubin, albumin and prothrombin time were essentially within the normal range in all patients Positive autoantibodies in low titres were found in 20% of patients including ANA in 15.4%, and ... after initiation of the prescribed lifestyle modification, 49% of children were able to lose at least 10% of their baseline weight, and 86% of them showed significant improvement or normalisation ... or diverticulitis Preoperative recognition of the infection is difficult and is found in ,10% of cases prior to surgery.3 Imaging modalities are non-specific, although CT or MRI may show the...
... Phase I clinical trial In vitro and in vivo Adenovirus Ad5/3-D24 Main result In vitro in vivo In vitro in vivo In vitro in vivo In vitro in vivo In vitro in vivo andandandandand Killing of ... therapy HSV-TK suicide gene therapy Reference Phase I/ II/III clinical trial Phase I/ II clinical trial Phase I clinical trial Phase I clinical trial Phase I clinical trial Phase I clinical trial ... Growth inhibition of E6-positive cells Cell killing of HPV-positive cells [69] [66] In vitro and in vivo In vitro and in vivo In vitro Inhibition of cervical cancer cell growth [67] Inhibition of...
... peritoneum Six hours later, the expression of inducible nitric oxide synthase (iNOS) mRNA increased in the liver Injection of DEP did not induce inflammation or oxidative damage to DNA in the ... alterations in insulin/insulin-like growth factor and insulin resistance, which contribute to fatty liver, an escalating trend in the incidence of pediatric NAFLD and its related complications ... 54 Kelishadi R et al Obesity and Air Pollution diagnosis, and pathogenesis of pediatric NAFLD, as well as the possible associations with obesity and air pollution, which are the adverse...
... removing the BglII and Cationic -Helical Peptides 13 HindIII insert of the plasmid PGV-C (Toyo Ink), and ligating with the BglII and HindIII fragment from the pRc/CMV (Invitrogen), which contains ... polyamidoamine dendrimer and polyethylenimine dendrimer have been tested for their potential utility and have exhibited high transfection efficiency in vitro and in vivo (2,3) However, these dendrimers ... The synthesis method is described as follows and is summarized in Fig 16 Niidome and Aoyagi Fig Gene transfer efficiencies of the peptides into several cell lines -Helical peptide portion can...
... vector is significantly increased Release and gel purification of the insert doesnot increase the recombination frequency, although this is a superior technique as there is no possibility of plasmid ... in vivo is illustrated in Fig Following primary cutaneous or mucosal inoculation, the virus undergoes lytic replication in the infected epithelia Viral particles are released at the site of the ... for Gene Therapy of Cystic Fibrosis and Other Genetic Diseases, University of Iowa College of Medicine, Iowa City, IA J GEORGE DICKSON • Division of Biochemistry, School of Biological Sciences,...
... of IFN activity The two phenotypes display diverse permissivity to adenoviral replication in vitro suggesting the practical implication that these signatures could facilitate the identification ... of ISGs In this study, we identified by transcriptional profiling two ISG-defined phenotypes of pancreatic cancer that are readily recognized by immunohistochemistry according to the expression ... instructions (Affymetrix) After in vitro transcription, labeling and fragmentation, probes were hybridized to the GeneChips that were then washed in a GeneChip Fluidics Station 400 (Affymetrix);...
... immunotherapy, autologous, allogeneic, and vaccine; we limited the search to trials enrolling adult patients and asked for all Phase I, II and III trials in the United States Of the listed trials, ... these possibilities, we propose the formation of immunotherapy consortiums that could provide the administrative and statistical oversight and immunologic endpoint integration needed and encourage ... http://www.celldextherapeutics.com/[57] has plans to conduct a Phase III trial to test EGFRvIII peptide vaccination if the results of their Phase II multiinstitutional trial conducted at sites in 15 states...
... In our studies, we mainly investigated the cytotoxicity andthe transfection efficiency of the three PEI derivatives (PCFC-g-PEI, FAPEAs and HPEI) in vitro and on a RCC model in vivo The toxicity ... positive controls in vitro Furthermore, the cross-linker IPDI stabilizes the polyplexes and prolongs circulation times at the same time [19] In addition, the relative smaller particle size and ... compatibility and a lower cytotoxicity than PEI (25kD):pVHL On the other hand, with an optimized weight ratio, the transfection efficiency of PCFC-g-PEI is also a little increased than 25-kD PEI...
... basiliximab will be administered for induction therapy as one key element of the institution’s immunosuppressive regimen There is a growing body of evidence indicating that basiliximab can impair ... score’ that aims to detect toxicities of the highest clinical significance that will halt the further development of this therapy option The most important consideration is that MAPCs might pool in ... Thus, we believe thatthe potential benefit of administering MAPCs to patients after allogeneic liver transplantation is significant andthatthe associated risks of the cell infusions are low and...